Objectives: There remains no consensus management for isolated distal deep vein thrombosis (IDDVT), with current data inconclusive and dating back to the warfarin era. In the current direct oral anticoagulant (DOAC) era, optimal management of IDDVT needs to be re-assessed. Methods: A retrospective evaluation of patients treated with therapeutic anticoagulation for IDDVT in the DOAC era (2013-2016) was compared with historically published data from the warfarin era (2011-2012). Results: 247 patients were evaluated, 103 from the DOAC era and 122 from the warfarin era. There were less provoked events in the DOAC cohort (45.6% vs 66.7%, p=<0.01). Overall rate of major bleeding was 1.6% with 1.0% in the DOAC era and 2.1% in the warfarin era (p=0.50). There was no difference in rates of VTE progression on treatment 5.8% vs 4.9% respectively (p=0.91). Overall risk of VTE recurrence post cessation was 5.3% (1.86 per 100 person years) with no difference between groups (5.8% vs 4.9%, p=0.74). Conclusions: Our data shows IDDVT is not always benign, with risk of extension despite treatment and long-term risk of VTE-recurrence. Therapeutic anticoagulation with DOAC in these patients was associated with a major bleeding rate of 1.0% in the DOAC cohort. Further clinical trials into the optimal IDDVT management in the DOAC era are necessary.